A continual interplay between neurons and their targets is fundamental to the development, maintenance and modification of synapses. Our long term goals are to identify molecules mediating these interactions and gain an understanding of their regulation. The neuromuscular systems provides a well characterized, relatively simple system in which to study these instructions. Recent studies of the neural cell adhesion molecule (N-CAM) suggest it plays an important role in nerve-muscle adhesion during synapse formation. Levels of N-CAM are regulated in turn by neural activity. By studying synapse formation in nerve-muscle co-cultures using variant cell lines deficient in N-CAM we will provide a more critical examination of the importance of N-CAM in neuromuscular synaptogenesis. Using specific antibodies and cDNA probes to N-CAM we will study the neural regulation of muscle N-CAM expression, and by molecular genetic analysis of selected N-CAM deficient variants we will identify genes required for N-CAM RNA accumulation. Finally, we will search for muscle specific differences in N-CAM structure which could play a role in selective synapse formation.